Derivatives of dipropylacetamido-2-pyrimidine

ABSTRACT

Dipropylacetamido pyrimidine and the nuclear substituted alkyl, benzyl, alkoxy, halo, halomethyl or halobenzyl derivatives are described as useful in the preparation of proteins and as radioprotective materials.

United States Patent Dardas 1 Aug. 29, 1972 [54] DERIVATIVES OFDlPROPYLACETAMIDO-2- [56] References Cited PYRIMIDINE OTHER PUBLICATIONS[72] Inventor: Anastasios Dardas, Grenoble,

France Benoit- Guyod, Chem. Abstracts, 70:86985e (1969).

[73] Assrgnee: Laboratories S.A., Primary Emmmer Alex Maze] am AssistantExaminer-R. J. Gallagher [22] Filed: March 30, 1970 Attomey-Mason,Kolehmainen, Rathbum & Wyss [21] Appl. No.. 23,988 ABSTRACT RelatedApplicafion Dipropylaeetamido pyrimidine and the nuclear sub-Continuation Of 561'. No. 675,067, stituted alkyl, benzyl, alkoxy, halo,halomethyl or l967,aba11d0nedhalobenzyl derivatives are described asuseful in the preparation of proteins and as radio-protective materi-[52] US. Cl. ..260/256.4 N, ZED/256.4 C, 260/999 815 [51] Int. Cl...C07d 51/42 [58] Field of Search ..260/256.4 N, 256.4 C 3 Claims, NoDrawings l DERIVATIVESOFDIPROPYLACETKNIIDO-Z- rvlmnmms CROSS-REFERENCETO CO-PEN'DING APPLICATION This application is a continuation of myoo-periding application Ser. No. 675,067 filed 'Oct. 1-3, 1967 nowabandoned.

GENERAL DESCRIPTION OF INVENTION The present invention relates to newcompositions which are dipropylacetan'iido-Lpyfimidine and derivativesthereof, corresponding -to the following formula:

formula:

i )qwc-b-olm which is the amide of dipropylacetic acid and 2 aminopyrimidine or dipropylacetamido pyrimidine.

These products can serve as intermediates in the synthesis in thepreparation of certain proteins as well as radio-protective materials.The unsubstituted product is useful as a tranquilizer, a hypnotic and apotentiator of tranquilizers and sedatives which use is the subject of apatent application Henry E. Meunier and Pierce L. Eymard Ser. No.675,063 filed Oct. l3, 1967, now abandoned in favor ofcontinuation-impart application Ser. No. 855,776, filed Sept. 5, 1969,now US. Pat. No. 3,558,781 issued Jan. 26, 1971.

For the preparation of the compounds of the invention one can proceed intwo difi'erent ways: either in the absence of solvent or in the presenceof pyridine. In either case the final product obtained gives the samemelting point, the same infrared spectrum and a similar spot in thinlayer chromatography; it is therefore the same product.

The following Examples are presented in order to disclose the inventionmore fully. It should be understood, however, that they are not intendedto limit the invention in any way.

EXAMPLE I In the process of synthesis without solvent, one can utilize,as starting materials, 2 moles of Z-aniino pyrimidine and 1 mole ofdipropylacetic acid chloride.

Thei'eaction can be represented by the following equation:

N 2 I Cl-GO-CPHCaHr):

In a preferred ma'nn'er of carrying out the invention, "the materialsare mixed and are heated for l at 60-70 C. Then an alkaline extractionwith ethyl ether is made, the base used being aqueous sodihydroxide. Theethereal phase, on evaporation, gives a product A which is purified byrecrystallization in fe 'thyl alcohol or ethyl ether.

The purity of the product is verified by thin layer chioiiiatog'i'aphy,the best system of chromatography fo'un'd being the following:

adsorbent Aluminum oxide G of Merck ellient Chlorofonn-acetone 8:2

developer Iodine vapor The melting point is 101 C. afterrecrystallization.

The analysis of the amide corresponding to the forniula C H ON, givesthe following results:

calculated C percent, 65.15; H percent, 8.5; N percent, l9.0;

found C percent, 65.08; H percent, 8.65; N percent, 19.09;

Also, the amide that is the object of the invention is characterized bymaking infrared spectra of 2-amino pyrimidine, of dipropylacetic acidand of product A, in chloroform. The spectrum of product A is difierentfrom those of the two others in that it presents:

A. The peaks for CH CH,, CH in the zone of 2,800cm' to 300cm which aredue to the grouping B. the peak of 3,400cm' which corresponds to NH C.the peaks at l,700cm" and l,670cm due to D. the large absorption peaktypical of primidine from 715cm to 800cm K On the other hand, the peaksof 3,450cm and l,6l0cmof NH, of the Z-amino pyrimidine no longer exist.

The obtained product A is therefore the following amide:

EXAMPLE II In the method of preparation in the presence of a solvent,the mixture of reactants is heated in pyridine for an hour at 60-70 C.After a partial evaporation of the pyridine under vacuum thehydrochloride of pyrimidine precipitates, the remainder is filtered andis evaporated. Thus is obtained a solid product that is recrystallizedin alcohol and which is designated as B. It shows the same meltingpoint, the same LR. spectrum and gives the same spot in thin layerchromatography as the product obtained in the absence of pyridine.Therefore, in both cases it is the same amide. The yield is 60 percentof the theoretical yield.

While the unsubstituted dipropylacetamido-Z- pyrimidine has beendescribed in Examples 1 and [I it is obvious that all of the substitutedcompounds of this invention as depicted in the general formula I can beprepared by reaction of dipropylacetic acid chloride and thecorresponding amino pyrimidine.

Others may practice the invention in any of the numerous ways which willbe suggested by this disclosure to one skilled in the art by employingone or more of the novel features disclosed or equivalents thereof.

I claim: 1. A compound of the formula:

2. The compound as defined in Claim 1 wherein at least one of R1, R2 andR3 are lower alkyl and the remaining ones are hydrogen, the number ofcarbon atoms in the lower alkyl radicals being between one and fourinclusive.
 3. The compound as defined in claim 1 wherein R1, R2 and R3are hydrogen.